tbuckley/cabot-search huggingface dataset:
Multifunctional Nanofibrous Scaffolds with Angle‐Ply Microstructure and Co‐Delivery Capacity Promote Partial Repair and Total Replacement of Intervertebral Disc
Authors: Feng Han, Qifan Yu, Genglei Chu, Jiaying Li, Zhuang Zhu, Zhengdong Tu, Changjiang Liu, Weidong Zhang, Runze Zhao, Haijiao Mao, Fengxuan Han, Bin Li
Journal: Advanced Healthcare Materials (2022)

There is an urgent clinical need for the treatment of annulus fibrosus (AF) impairment caused by intervertebral disc (IVD) degeneration or surgical injury. Although repairing injured AF through tissue engineering is promising, the approach is limited by the complicated angle-ply microstructure, inflammatory microenvironment, poor self-repairing ability of AF cells and deficient matrix production. In this study, electrospinning technology is used to construct aligned core-shell nanofibrous scaffolds loaded with transforming growth factor-β3 (TGFβ3) and ibuprofen (IBU), respectively. The results confirm that the rapid IBU release improves the inflammatory microenvironment, while sustained TGFβ3 release enhances nascent extracellular matrix (ECM) formation. Biomaterials for clinical applications must repair local AF defects during herniectomy and enable AF regeneration during disc replacement, so a box defect model and total IVD replacement model in rat tail are constructed. The dual-drug delivering electrospun scaffolds are assembled into angle-ply structure to form a highly biomimetic AF that is implanted into the box defect or used to replace the disc. In two animal models, it is found that biomimetic scaffolds with good anti-inflammatory ability enhance ECM formation and maintain the mechanical properties of IVD. Findings from this study demonstrate that the multifunctional nanofibrous scaffolds provide inspirations for IVD repair.
Safety and Efficacy of 90Y-FAPI-46 Radioligand Therapy in Patients with Advanced Sarcoma and Other Cancer Entities
Authors: Wolfgang P. Fendler, Kim M. Pabst, Lukas Kessler, Pedro Fragoso Costa, Justin Ferdinandus, Manuel Weber, Maria Lippert, Katharina Lueckerath, Lale Umutlu, Karina Kostbade, Ilektra A. Mavroeidi, Martin Schuler, Marit Ahrens, Christoph Rischpler, Sebastian Bauer, Ken Herrmann, Jens T. Siveke, Rainer Hamacher
Journal: Clinical Cancer Research (2022)

Abstract Purpose: We report efficacy and safety of 90Y-labeled FAPI-46 (90Y-FAPI-46-RLT) in patients with advanced sarcoma, pancreatic cancer, and other cancer entities. Experimental Design: Up to four cycles of radioligand therapy (RLT) were offered to patients with (i) progressive metastatic malignancy, (ii) exhaustion of approved therapies, and (iii) high fibroblast activation protein (FAP) expression, defined as SUVmax ≥ 10 in more than 50% of tumor. Primary endpoint was RECIST response after RLT. Secondary endpoints included PET response (PERCIST), overall survival (OS), dosimetry, and safety of FAP-RLT. Results: Among 119 screened patients, 21 (18%) were found eligible [n = 16/3/1/1 sarcoma/pancreatic cancer/prostate/gastric cancer; 38% Eastern Cooperative Oncology Group (ECOG) ≥ 2] and received 47 90Y-FAPI-46-RLT cycles; 16 of 21 (76%) patients underwent repeat RLT. By RECIST, disease control was confirmed in 8 of 21 patients [38%; 8/16 (50%) of evaluable patients). There was one partial response (PR) and seven stable diseases after RLT. Disease control was associated with prolonged OS (P = 0.013). PERCIST response was noted in 8 of 21 patients [38%; 8/15 (53%) of evaluable patients]. Dosimetry was acquired in 19 (90%) patients. Mean absorbed dose was 0.53 Gy/GBq in kidney, 0.04 Gy/GBq in bone marrow, and &amp;lt;0.14 Gy/GBq in liver and lung. Treatment-related grade 3 or 4 adverse events were observed in 8 (38%) patients with thrombocytopenia (n = 6) and anemia (n = 6) being most prevalent. Conclusions: 90Y-FAPI-46-RLT was safe and led to RECIST PR in one case as well as stable disease in about one third of patients with initially progressive sarcomas, pancreatic cancer, and other cancers. Discontinuation after the first cycle and a low rate of PR requires future improvement of FAP-RLT.
Pre-encoded responsiveness to type I interferon in the peripheral immune system defines outcome of PD1 blockade therapy
Authors: Giselle M. Boukhaled, Ramy Gadalla, Heidi J. Elsaesser, Diala Abd-Rabbo, Rene Quevedo, S. Y. Cindy Yang, Mengdi Guo, Ben X. Wang, Babak Noamani, Diana Gray, Sally C. M. Lau, Kirsty Taylor, Kyaw Aung, Anna Spreafico, Aaron R. Hansen, Samuel D. Saibil, Naoto Hirano, Cynthia Guidos, Trevor J. Pugh, Tracy L. McGaha, Pamela S. Ohashi, Adrian G. Sacher, Marcus O. Butler, David G. Brooks
Journal: Nature Immunology (2022)
Population-Level Impact and Cost-effectiveness of Continuous Glucose Monitoring and Intermittently Scanned Continuous Glucose Monitoring Technologies for Adults With Type 1 Diabetes in Canada: A Modeling Study
Authors: Michael A. Rotondi, Octavia Wong, Michael Riddell, Bruce Perkins
Journal: Diabetes Care (2022)

OBJECTIVE Maintaining healthy glucose levels is critical for the management of type 1 diabetes (T1D), but the most efficacious and cost-effective approach (capillary self-monitoring of blood glucose [SMBG] or continuous [CGM] or intermittently scanned [isCGM] glucose monitoring) is not clear. We modeled the population-level impact of these three glucose monitoring systems on diabetes-related complications, mortality, and cost-effectiveness in adults with T1D in Canada. RESEARCH DESIGN AND METHODS We used a Markov cost-effectiveness model based on nine complication states for adults aged 18–64 years with T1D. We performed the cost-effectiveness analysis from a single-payer health care system perspective over a 20-year horizon, assuming a willingness-to-pay threshold of CAD 50,000 per quality-adjusted life-year (QALY). Primary outcomes were the number of complications and deaths and the incremental cost-effectiveness ratio (ICER) of CGM and isCGM relative to SMBG. RESULTS An initial cohort of 180,000 with baseline HbA1c of 8.1% was used to represent all Canadians aged 18–64 years with T1D. Universal SMBG use was associated with ∼11,200 people (6.2%) living without complications and ∼89,400 (49.7%) deaths after 20 years. Universal CGM use was associated with an additional ∼7,400 (4.1%) people living complications free and ∼11,500 (6.4%) fewer deaths compared with SMBG, while universal isCGM use was associated with ∼3,400 (1.9%) more people living complications free and ∼4,600 (2.6%) fewer deaths. Relative to SMBG, CGM and isCGM had ICERs of CAD 35,017/QALY and 17,488/QALY, respectively. CONCLUSIONS Universal use of CGM or isCGM in the Canadian T1D population is anticipated to reduce diabetes-related complications and mortality at an acceptable cost-effectiveness threshold.
Targeted Recruitment and Degradation of Estrogen Receptor <i>α</i> by Photothermal Polydopamine Nanoparticles for Breast Tumor Ablation
Authors: Yu Zhang, Xin Ding, Fei Xie, Mingjie Gao, Julu Qiu, Ziwei Wang, Luolong Qing, Jiaqi Yan, Na Peng, Yuanyuan Li, Juan Xu, Qi Cai, YuHua Jin, Yuanhong Jiao, Yi Liu, Huan He, Silong Zhang
Journal: Advanced Healthcare Materials (2022)

Abstract The major challenges of photothermal therapy (PTT) toward clinical application are the severe skin injury and inflammation response associated with high power laser irradiation. Herein, polydopamine nanoparticles (PDA‐EST and PDA‐RAL) targeted to estrogen receptor α (ER α ) for efficient ablation of breast tumor under a low irradiation density of 0.1 W cm –2 are reported. These nanoparticles are capable of recruiting ER α on their surface and induce a complete ER α degradation via localized heat. Owing to the ER α targetability, PDA‐EST and PDA‐RAL strongly suppress the proliferation of breast cancer cells without causing significant inflammation. This work provides a generalized method for enhancing PTT efficacy under low irradiation density.
Reply
Authors: Tolga Gidener, Ross Dierkhising, Kristin C. Mara, Terry M. Therneau, Sudhakar K. Venkatesh, Richard L. Ehman, Meng Yin, Alina M. Allen
Journal: Hepatology (2022)

The authors thank Dr. Reiberger et al. for their interest and valuable comments on our manuscript. The potential limitations imposed by the retrospective nature of this study were acknowledged. However, we want to clarify that MR elastography (MRE) has been available at the Mayo Clinic since 2007 and routinely used for initial staging and longitudinal monitoring of liver fibrosis. Until ultrasound‐based elastography was added to the practice in 2014 and primarily used for non‐NAFLD cases due to body mass index–related limitations, the only alternative was liver biopsy, which is sparsely used. The spectrum of disease severity at baseline MRE shows that repeat assessment was performed across all stages, not preferentially in advanced disease. Second, we agree with the sample size comments. Given the slow disease progression, the incidence of cirrhosis was 4%. By extrapolation, at least 1000 subjects with NAFLD, each with at least two MREs, or longer follow‐up would be needed to detect 40 incident cirrhosis cases. Future studies of this caliber will be available, but waiting for those will miss timely opportunities to learn about the role of MRE. Third, no risk factor was significantly associated with changes in liver stiffness measurement (LSM). The association with hypertension was the closest to the significance threshold (p = 0.08). It would be inaccurate to speculate hypertension as causative reason without a controlled setting. More studies, controlled for other risk factors, would be needed to explore such a relationship. Fourth, to explore the relationship of longitudinal LSM changes with steatohepatitis, baseline liver biopsies would be needed in every patient. The study goal was to explore the clinical applicability of prognostic noninvasive markers, to avoid biopsies for disease monitoring. The 24 subjects developed an event of interest after the first, but before subsequent, MREs, and it would not have been statistically sound to include them in the outcome analysis. Finally, while we agree that similar studies investigating the prognostic role of vibration‐controlled transient elastography are warranted, this does not eliminate the importance of studying the role of MRE and its use where available. MRE remains the most accurate, noninvasive test for liver fibrosis and longitudinal changes in liver stiffness.1 Its clinical role is increasingly being recognized in clinical guidelines, especially in NAFLD.2 The limitations of availability and cost should be balanced against diagnostic performance and clinical value. MRE is already deployed at over 2000 locations worldwide, and the current average Medicare cost in the United States is $170.3
Case 21-2022: A 17-Year-Old Girl with Fever and Cough
Authors: Mary C. Ottolini, Randheer Shailam, Amita Sharma, Ivy A. Rosales
Journal: New England Journal of Medicine (2022)

A 17-year-old girl was admitted because of prolonged fever and cough. She had an elevated creatinine level and a low hemoglobin level. A diagnostic test was performed.
Hurricanes and Mortality among Patients Receiving Dialysis
Authors: Matthew F. Blum, Yijing Feng, G. Brooke Anderson, Dorry L. Segev, Mara McAdams-DeMarco, Morgan E. Grams
Journal: Journal of the American Society of Nephrology (2022)

Hurricanes are severe weather events that can disrupt power, water, and transportation systems. These disruptions may be deadly for patients requiring maintenance dialysis. We hypothesized that the mortality risk among patients requiring maintenance dialysis would be increased in the 30 days after a hurricane.Patients registered as requiring maintenance dialysis in the United States Renal Data System who initiated treatment between January 1, 1997 and December 31, 2017 in one of 108 hurricane-afflicted counties were followed from dialysis initiation until transplantation, dialysis discontinuation, a move to a nonafflicted county, or death. Hurricane exposure was determined as a tropical cyclone event with peak local wind speeds ≥64 knots in the county of a patient's residence. The risk of death after the hurricane was estimated using time-varying Cox proportional hazards models.The median age of the 187,388 patients was 65 years (IQR, 53-75) and 43.7% were female. There were 27 hurricanes and 105,398 deaths in 529,339 person-years of follow-up on dialysis. In total, 29,849 patients were exposed to at least one hurricane. Hurricane exposure was associated with a significantly higher mortality after adjusting for demographic and socioeconomic covariates (hazard ratio, 1.13; 95% confidence interval, 1.05 to 1.22). The association persisted when adjusting for seasonality.Patients requiring maintenance dialysis have a higher mortality risk in the 30 days after a hurricane.
Author Correction: Spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals
Authors: Andrea Brizzi, Charles Whittaker, Luciana M. S. Servo, Iwona Hawryluk, Carlos A. Prete, William M. de Souza, Renato S. Aguiar, Leonardo J. T. Araujo, Leonardo S. Bastos, Alexandra Blenkinsop, Lewis F. Buss, Darlan Candido, Marcia C. Castro, Silvia F. Costa, Julio Croda, Andreza Aruska de Souza Santos, Christopher Dye, Seth Flaxman, Paula L. C. Fonseca, Victor E. V. Geddes, Bernardo Gutierrez, Philippe Lemey, Anna S. Levin, Thomas Mellan, Diego M. Bonfim, Xenia Miscouridou, Swapnil Mishra, Mélodie Monod, Filipe R. R. Moreira, Bruce Nelson, Rafael H. M. Pereira, Otavio Ranzani, Ricardo P. Schnekenberg, Elizaveta Semenova, Raphael Sonabend, Renan P. Souza, Xiaoyue Xi, Ester C. Sabino, Nuno R. Faria, Samir Bhatt, Oliver Ratmann
Journal: Nature Medicine (2022)
Withdrawing volatile anaesthetic agents limits options for patients, particularly women and children
Authors: Mark W Davies
Journal: BMJ (2022)

In heart failure (HF), the impaired left ventricular (LV) arterial coupling and diastolic dysfunction present at rest are exacerbated during exercise. C-type natriuretic peptide (CNP) is elevated in HF. However, its functional effects are unclear. We tested the hypotheses that CNP with vasodilating, natriuretic, and positive inotropic and lusitropic actions may prevent this abnormal exercise response after HF. We determined the effects of CNP (2 μg/kg plus 0.4 μg/kg/min, iv, 20 min) on plasma levels of cGMP before and after HF and assessed LV dynamics during exercise in 10 chronically-instrumented dogs with pacing-induced HF. We found that compared with before HF, CNP infusion caused significantly greater increases in cGMP levels after HF. After HF, at rest, CNP administration significantly reduced LV end-systolic pressure (PES), arterial elastance (EA) and end-diastolic pressure. The peak mitral flow (dV/dtmax) was also increased due to decreased minimum LVP (LVPmin) and the time constant of LV relaxation (τ) (p&lt;0.05). In addition, LV contractility (EES) was increased. The LV-arterial coupling (EES/EA) was improved. The beneficial effects persisted during exercise. Compared with exercise in HF preparation, treatment with CNP caused significantly less increases in PES, but significantly decreased τ (34.2 vs 42.6 ms) and LVPmin with further augmented dV/dtmax. Both EES, EES/EA (0.87 vs 0.32) were increased. LV mechanical efficiency improved from 0.38 to 0.57 (p&lt;0.05). After HF, exogenous CNP produces arterial vasodilatation and augments LV contraction, relaxation, diastolic filling and LV arterial coupling, thus improving LV performance at rest and restoring normal exercise responses after HF.
Remnant Cholesterol and Its Visit-to-Visit Variability Predict Cardiovascular Outcomes in Patients With Type 2 Diabetes: Findings From the ACCORD Cohort
Authors: Liyao Fu, Shi Tai, Jiaxing Sun, Ningjie Zhang, Ying Zhou, Zhenhua Xing, Yongjun Wang, Shenghua Zhou
Journal: Diabetes Care (2022)

OBJECTIVE Remnant cholesterol (remnant-C) predicts atherosclerotic cardiovascular disease, regardless of LDL-cholesterol (LDL-C) levels. This study assessed the associations between remnant-C and cardiovascular outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS This post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial used patient (type 2 diabetes &amp;gt;3 months) remnant-C and major adverse cardiovascular event (MACE) data from the study database. The associations between remnant-C and MACEs were evaluated using Cox proportional hazards regression analyses. We examined the relative MACE risk in remnant-C versus LDL-C discordant/concordant groups using clinically relevant LDL-C targets by discordance analyses. RESULTS The baseline analysis included 10,196 participants, with further visit-to-visit variability analysis including 9,650 participants. During follow-up (median, 8.8 years), 1,815 patients (17.8%) developed MACEs. After adjusting for traditional cardiovascular risk factors, each 1-SD increase in remnant-C was associated with a 7% higher MACE risk (hazard ratio [HR] 1.07, 95% CI 1.02–1.12, P = 0.004). In the fully adjusted model, the visit-to-visit remnant-C variability calculated using logSD (HR 1.41, 95% CI 1.18–1.69, P &amp;lt; 0.001) and logARV (HR 1.45, 95% CI 1.22–1.73, P &amp;lt; 0.001) was associated with MACEs. Residual lipid risk (remnant-C ≥31 mg/dL) recognized individuals at a higher MACE risk, regardless of LDL-C concentrations. Within each LDL-C subgroup (&amp;gt;100 or ≤100 mg/dL), high baseline remnant-C was associated with a higher MACE risk (HR 1.37, 95% CI 1.09–1.73, P = 0.007; HR 1.22, 95% CI 1.04–1.41, P = 0.015, respectively). CONCLUSIONS Remnant-C levels were associated with MACEs in patients with type 2 diabetes independent of LDL-C, and visit-to-visit remnant-C variability helped identify those with higher cardiovascular risk.
Patient-Proxy and Societal Perspectives of Quality-of-Life Utilities in Children With Cleft Lip and Palate Managed With Surgical Repair vs No Repair in Ethiopia
Authors: Karen Y. Chung, Gebremedhin B. Gebretekle, Andrew Howard, Eleanor Pullenayegum, Mekonen Eshete, Christopher R. Forrest, Beate Sander
Journal: JAMA Network Open (2022)

In Ethiopia, more than 70% of infants with cleft lip and/or palate (CL/P) lack access to surgery. Infants who are untreated can experience severe malnutrition and extreme social stigma resulting in abandonment. Utilities are standardized measures of health-related quality of life (HRQOL) that inform health care resource allocation. However, CL/P utilities are missing from low- and middle-income countries (LMICs).To elicit utilities for untreated and surgically treated children with CL/P with consideration for social determinants of health from patient-proxy and societal participants.This cross-sectional study used patient proxies and societal participants in Addis Ababa, Ethiopia, from July 1, 2019, to January 30, 2020. Eligible patient proxies were caregivers of children younger than 18 years with nonsyndromic CL/P who were untreated or received surgery. Proxies were necessary as most patients were 0 to 4 years old and cannot reliably self-report. Eligible societal participants were 18 years and older with no family history of CL/P.Surgical treatment and social determinants of health.Participants measured utilities using the visual analog scale (VAS), time trade-off (TTO), and standard gamble (SG).In this study, 312 patient proxies and 135 societal participants were recruited. Mean (SD) utilities for untreated CL/P ranged from 0.57 (0.23) to 0.70 (0.22) from patient proxies and from 0.35 (0.21) to 0.8 (0.23) from societal participants, depending on utility instrument and cleft type. Surgical treatment was associated with a better HRQOL from the patient-proxy perspective (VAS, 0.17; 95% CI, 0.09 to 0.26; TTO, 0.15; 95% CI, 0.05 to 0.25) from the societal perspective (VAS, 0.21; 95% CI, 0.16 to 0.26; TTO, 0.17; 95% CI, 0.13 to 0.22; SG, 0.11; 95% CI, 0.06 to 0.15). Social determinants of health that were associated with patient-proxy utilities were income above the national mean (VAS, 0.10; 95% CI, 0.02 to 0.17; TTO, 0.11; 95% CI, 0.02 to 0.20), and religion (Christian vs other: TTO, -0.10; 95% CI, -0.17 to -0.03). From the societal perspective, the association between treatment and utilities was smaller in females compared with males (TTO, -0.05; 95% CI, -0.10 to -0.01).The findings of this study suggest that CL/P disease severity and surgical impact in Ethiopia were undervalued by previous estimates from high-income countries and were associated with social determinants of health. Utility studies from participants from LMICs are feasible and necessary for representing HRQOL in LMICs and addressing health inequalities.
Human β-defensin-3 attenuates atopic dermatitis–like inflammation through autophagy activation and the aryl hydrocarbon receptor signaling pathway
Authors: Ge Peng, Saya Tsukamoto, Risa Ikutama, Hai Le Thanh Nguyen, Yoshie Umehara, Juan V. Trujillo-Paez, Hainan Yue, Miho Takahashi, Takasuke Ogawa, Ryoma Kishi, Mitsutoshi Tominaga, Kenji Takamori, Jiro Kitaura, Shun Kageyama, Masaaki Komatsu, Ko Okumura, Hideoki Ogawa, Shigaku Ikeda, François Niyonsaba
Journal: Journal of Clinical Investigation (2022)

Human β-defensin-3 (hBD-3) exhibits antimicrobial and immunomodulatory activities; however, its contribution to autophagy regulation remains unclear, and the role of autophagy in the regulation of the epidermal barrier in atopic dermatitis (AD) is poorly understood. Here, keratinocyte autophagy was restrained in the skin lesions of patients with AD and murine models of AD. Interestingly, hBD-3 alleviated the IL-4– and IL-13–mediated impairment of the tight junction (TJ) barrier through keratinocyte autophagy activation, which involved aryl hydrocarbon receptor (AhR) signaling. While autophagy deficiency impaired the epidermal barrier and exacerbated inflammation, hBD-3 attenuated skin inflammation and enhanced the TJ barrier in AD. Importantly, hBD-3–mediated improvement of the TJ barrier was abolished in autophagy-deficient AD mice and in AhR-suppressed AD mice, suggesting a role for hBD-3–mediated autophagy in the regulation of the epidermal barrier and inflammation in AD. Thus, autophagy contributes to the pathogenesis of AD, and hBD-3 could be used for therapeutic purposes.
The Continued Struggle for Defining a Role for Radiotherapy in Pancreas Cancer
Authors: Daniel H. Ahn, Tanios Bekaii-Saab
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Efficacy of Preoperative mFOLFIRINOX vs mFOLFIRINOX Plus Hypofractionated Radiotherapy for Borderline Resectable Adenocarcinoma of the Pancreas
Authors: Matthew H. G. Katz, Qian Shi, Jeff Meyers, Joseph M. Herman, Michael Chuong, Brian M. Wolpin, Syed Ahmad, Robert Marsh, Larry Schwartz, Spencer Behr, Wendy L. Frankel, Eric Collisson, James Leenstra, Terence M. Williams, Gina Vaccaro, Alan Venook, Jeffrey A. Meyerhardt, Eileen M. O’Reilly
Journal: JAMA Oncology (2022)

National guidelines endorse treatment with neoadjuvant therapy for borderline resectable pancreatic ductal adenocarcinoma (PDAC), but the optimal strategy remains unclear.